It has been demonstrated that the cryptobiotic state of spores in Agaricus bisporus is initiated through inhibition of key metabolic pathways by derivatives of a low molecular weight phenol, gamma-L-glutaminyl-4-hydroxybenzene (GHB). This phenol has been isolated; its molecular structure characterized, and synthesis has been achieved. In the natural system, oxidation of GHB is accomplished by a tyrosinase, that yields a hydroxybenzoquinone and an oxidation product which together markedly suppress mitochondrial energy production and the synthesis of proteins and nucleic acids. In in vitro systems these inhibitors strongly suppress thymidine, uracil and amino acid incorporation by neoplastic cells. The present studies will evaluate the potential therapeutic anti-tumor properties of these metabolic inhibitors and their analogues, specifically in regards to tumor cell systems, such as melanocarcinoma, that contain tyrosinase and conceptually have the potential to intracellularly convert GHB to active inhibitors, thus targeting cytotoxicity and minimizing systemic toxicity to the host. BIBLIOGRAPHIC REFERENCES: Vogel, F.S., Kemper, L.A.K., Jeffs, P.W., Cass, M.W., and Graham, D.G. Gamma-L-glutaminyl-4-hydroxybenzene, an inducer of cryptobiosis in Agaricus bisporus and a source of specific metabolic inhibitors for melanogenic cells. Cancer. Res. 37:1133-1136, 1977. Graham, D.G., Tye, R.W., and Vogel, F.S. Inhibition of DNA polymerase from L1210 murine leukemia by a sulfhydryl reagent from Agaricus bisporus. Cancer Res. 37:436-439, 1977.